The studies outlined in this proposal are a continuation of our effort to provide needed information on the mechanisms underlying the formation of cholesterol gallstones in man. We have undertaken to develop a multicompartmental kinetic system to describe cholesterol metabolism in man in a more precise manner than has been previously available. The studies outlined in this proposal are an attempt to provide the necessary information on the nature and characteristics of this hepatic-plasma cholesterol compartmental system. The application of this kinetic system (turnover rate constants, pool sizes and flow rates) to cholesterol metabolism in man could provide a basis for attacking a number of important problems in lipid metabolism. This technique will be useful for obtaining information on the partitioning of newly synthesized cholesterol between the various hepatic precursor pools and also to ascertain the relative contribution the plasma makes to the hepatic cholesterol compartments. The initial studies will use the T-tube bile fistula patient as model to develop the multicompartmental system and then this system will be applied to subjects with an intact enterohepatic circuit. It is also hoped that in the near future it will be possible to explore the metabolism of cholesterol in man in greater depth with particular emphasis on the bile acid and cholesterol feedback mechanisms. Our ultimate goal is to study aberrations in lipid metabolism which are associated with a number of disease state such as cholesterol gallstones, Type II and Type IV hyperlipoproteinemias, obesity, etc.